The origin of B cell recurrent chromosomal translocations: proximity versus DNA damage.
The origin of B cell recurrent chromosomal translocations: proximity versus DNA damage.
复制标题
B 细胞反复染色体易位的起源：邻近与 DNA 损伤。
DOI：
10.1016/j.molcel.2013.07.020
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发表时间：
2013
期刊：
影响因子：
16
通讯作者：
Nussenzweig,MichelC
中科院分区：
文献类型：
--
作者：
Casellas,Rafael;Resch,Wolfgang;Hakim,Ofir;Nussenzweig,MichelC
B cell lymphomas are characterized by recurrent chromosomal translocations. Why these events are so prevalent is an area of active investigation. Several ideas have been put forward to try to explain this phenomenon, including nuclear proximity between translocating genes, repeated DNA damage by enzymes that mediate Ig gene recombination (AID and RAGs), and selection for deregulated oncogenes.To test the contribution of these parameters, the Alt and Nussenzweig laboratories developed genome-wide techniques to map chromosomal rearrangements (Chiarle et al., 2011; Klein et al., 2011), and the Casellas laboratory developed a method to measure AID-mediated damage (Hakim et al., 2012; Yamane et al., 2013). Genomic interactions were computed either by 4C or Hi-C. These studies uncovered two kinds of translocations: AID-or RAG-dependent and independent. Translocations that occur in the absence of recurrent DNA damage (eg, AID À/À) are widespread and join interacting loci that are epigenetically accessible. The location and frequency of these events correlate with nuclear interactions (Hakim et al., 2012). Furthermore, because these events are randomly and broadly distributed across the genome (Figure S1A), they cannot be subtracted from sample to sample. In the presence of AID, $90% of translocations in trans recapitulate those obtained in AID À/À, in both their distribution and frequency. In contrast, the remaining 10% are AID dependent, ie, they are recurrent and can be subtracted between samples
